cancers Review Perioperative Management of Complex Hepatectomy for Colorectal Liver Metastases: The Alliance between the Surgeon and the Anesthetist Enrico Giustiniano 1,*, Fulvio Nisi 1,*, Laura Rocchi 1, Paola C. Zito 1, Nadia Ruggieri 1, Matteo M. Cimino 2, Guido Torzilli 2,3 and Maurizio Cecconi 1,3 1 Department of Anesthesia and Intensive Care Units, IRCCS Humanitas Research Hospital, 20089 Milan, Italy; [email protected] (L.R.); [email protected] (P.C.Z.); [email protected] (N.R.); [email protected] (M.C.) 2 Hepato-Biliary & Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, 20089 Milan, Italy; [email protected] (M.M.C.); [email protected] (G.T.) 3 Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy * Correspondence: [email protected] (E.G.); [email protected] (F.N.); Tel.: +39-02-8224-7459 (E.G.); +39-02-8224-4115 (F.N.); Fax: +39-02-8224-4190 (E.G. & F.N.) Simple Summary: Major high-risk surgery (HRS) exposes patients to potential perioperative adverse events. Hepatic resection of colorectal metastases can surely be included into the HRS class of operations. Limiting such risks is the main target of the perioperative medicine. In this context the Citation: Giustiniano, E.; Nisi, F.; collaboration between the anesthetist and the surgeon and the sharing of management protocols is Rocchi, L.; Zito, P.C.; Ruggieri, N.; of utmost importance and represents the key issue for a successful outcome. In our institution, we Cimino, M.M.; Torzilli, G.; Cecconi, M. Perioperative Management of have been adopting consolidated protocols for patients undergoing this type of surgery for decades; Complex Hepatectomy for Colorectal this made our mixed team (surgeons and anesthetists) capable of achieving a safe outcome for the Liver Metastases: The Alliance majority of our surgical population. In this narrative review, we report the most recent state of the art between the Surgeon and the of perioperative management of hepatic resection of colorectal metastases along with our experience Anesthetist. Cancers 2021, 13, 2203. in this field, trying to point out the main issues. https://doi.org/10.3390/ cancers13092203 Abstract: Hepatic resection has been widely accepted as the first choice for the treatment of colorectal metastases. Liver surgery has been recognized as a major abdominal procedure; it exposes patients Academic Editors: Giovanni Mauri, to a high risk of perioperative adverse events. Decision sharing and the multimodal approach to the Lorenzo Monfardini, patients’ management are the two key items for a safe outcome, even in such a high-risk surgery. This Matteo Donadon and Guido Torzilli review aims at addressing the main perioperative issues (preoperative evaluation; general anesthesia and intraoperative fluid management and hemodynamic monitoring; intraoperative metabolism; Received: 8 March 2021 administration policy for blood-derivative products; postoperative pain control; postoperative Accepted: 30 April 2021 Published: 3 May 2021 complications), in particular, from the anesthetist’s point of view; however, only an alliance with the surgery team may be successful in case of adverse events to accomplish a good final outcome. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in Keywords: liver surgery; colorectal; hepatic resection; perioperative care published maps and institutional affil- iations. 1. Introduction Hepatic resection has been widely accepted as the first choice for the treatment of Copyright: © 2021 by the authors. colorectal metastases [1]. Colorectal cancer often causes metastases to the liver (14–70% of Licensee MDPI, Basel, Switzerland. patients), of which modern surgery combined with neo-adjuvant chemotherapy permits This article is an open access article the resection both by open and laparoscopic surgery [2]. Hepatic surgery is considered a distributed under the terms and major surgery (MS); as such, it exposes patients to the risk of postoperative complications. conditions of the Creative Commons Furthermore, given the increasing number of subjects who undergo high-risk surgery Attribution (CC BY) license (https:// in old age along with age-related comorbidities, the risk of postoperative complications creativecommons.org/licenses/by/ further increases. 4.0/). Cancers 2021, 13, 2203. https://doi.org/10.3390/cancers13092203 https://www.mdpi.com/journal/cancers Cancers 2021, 13, 2203 2 of 19 Enhanced Recovery After Surgery (ERAS) programs ameliorated the perioperative course of major abdominal surgery. In particular, for digestive tract surgery, specific guidelines became available in the past decade (see www.erassociety.org, (Accessed on 2 February 2021) [3,4]. Modern surgery cannot ignore the need in a multimodal approach to prepare patients to high-risk surgery. The best way to ensure a safe outcome is to start making use of each specialist doctor who manages each aspect according to specific competences before the operation and continue this practice in the postoperative period. Our review tried to take stock of the anesthetic aspects of hepatic resection without forgetting the potential surgical adverse events, focusing on the closest perioperative period as follows: (1) preoperative evaluation and examinations; (2) general anesthesia and intraoperative fluid management and hemodynamic monitoring; (3) intraoperative alterations of metabolism and their treatment; (4) administration of blood-derivative products; (5) postoperative pain control; (6) postoperative complications. 2. Preoperative Considerations Preoperative assessment was adapted to individual patients and types of surgical resection. Young patients (<40 years) without underlying liver disease could undergo significant liver resection having the same preoperative work out of any major intra- abdominal operation. Conversely, patients with hepatic disease have an increased risk of intra- and postoperative complications and require an in-depth preoperative assessment. During the past decades, the liver surgery-associated mortality has reduced to less than 2% in referral centers, but the rate of postoperative adverse events is still high (20–50%)[5–7]. To quantify the operation-related risk, many score systems have been used. Despite the ASA (American Society of Anesthesiology physical status classification system) score being a simple tool adopted all over the world to evaluate patients preop- eratively, it does not take into account the type of operation the patient undergoes. In 2014, the European Society of Cardiology/European Society of Anesthesiology (ESC/ESA) guidelines on non-cardiac surgery recommended a healthy lifestyle and the correction of unstable clinical conditions to make patients arrive to the surgical theater with a sufficient functional capacity [8,9]. The DASI (Duke Activity Status Index) should be a reliable system of evaluating and predicting the postoperative outcome, in particular, adverse cardiac events [10]. Finally, the surgical Apgar score (SAS), even though it is not so widely used, could be a complementary reliable and simple system for estimating the risk of a poor postoperative outcome [11]. At any rate, the preoperative period should ameliorate the starting clinical conditions of patients, aiming at better results of the perioperative period. The ERAS Society recently released guidelines for fast-track management of patients undergoing liver surgery. The recommendations for the perioperative management of patients could be summarized as described below. (1) Recommended preoperative fasting of 6 h for solids and 2 h for liquids. Carbohydrate supplies may be used the evening before surgery and at least 2 h before anesthesia induction. (2) Short-acting anxiolytic drugs should be preferred over the long-acting ones to facilitate regional anesthesia prior to the surgery. (3) Administration of low-molecular-weight heparin (LMWH) or unfractionated heparin should start 2–12 h before the surgery aiming at reducing the risk of thromboembolism. (4) Minimally invasive procedures should be preferred where possible. (5) Maintenance of intraoperative normothermia. (6) Early oral intake at the first postoperative day and early mobilization (as soon as possible). (7) Routine epidural analgesia (EA) cannot be recom- mended for open liver surgery for ERAS patients. Wound infusion catheter or intrathecal opiates can be good alternatives combined with multimodal analgesia. (8) Prevention of postoperative nausea and vomiting (PONV). (9) Fluid management includes the central venous pressure (CVP) guide with a target < 5 cm H2O. (10) Steroids (methylprednisolone) may be used before hepatectomy in normal liver parenchyma since it decreases liver injury Cancers 2021, 13, 2203 3 of 19 and intraoperative stress without increasing the risk of complications. (11) Glycaemia control [4]. Cardiac function evaluation should assess the ability of the system to cope with the hemodynamic challenge of vascular exclusion during liver resection. Exercise or stress echocardiography may be useful to assess the contractile reserve. Relevant anamnestic data are those regarding previous neo-adjuvant chemotherapy, which may reduce functional cardiac reserve, and/or conditions causing elevation of central venous pressure (CVP) that significantly increase the risk of intraoperative bleeding [1]. Pulmonary evaluation focuses on detecting impaired pulmonary gas exchange or inadequate ventilatory reserve. Pulmonary